title: Dopaminergic function in cannabis users and its relationship to cannabis-induced psychotic symptoms.
abstract: BACKGROUND
  Cannabis is the most widely used illicit drug globally, and users are at increased risk of mental illnesses including psychotic disorders such as schizophrenia. Substance dependence and schizophrenia are both associated with dopaminergic dysfunction. It has been proposed, although never directly tested, that the link between cannabis use and schizophrenia is mediated by altered dopaminergic function.
  
  
  METHODS
  We compared dopamine synthesis capacity in 19 regular cannabis users who experienced psychotic-like symptoms when they consumed cannabis with 19 nonuser sex- and age-matched control subjects. Dopamine synthesis capacity (indexed as the influx rate constant [Formula: see text] ) was measured with positron emission tomography and 3,4-dihydroxy-6-[(18)F]-fluoro-l-phenylalanine ([(18)F]-DOPA).
  
  
  RESULTS
  Cannabis users had reduced dopamine synthesis capacity in the striatum (effect size: .85; t36 = 2.54, p = .016) and its associative (effect size: .85; t36 = 2.54, p = .015) and limbic subdivisions (effect size: .74; t36 = 2.23, p = .032) compared with control subjects. The group difference in dopamine synthesis capacity in cannabis users compared with control subjects was driven by those users meeting cannabis abuse or dependence criteria. Dopamine synthesis capacity was negatively associated with higher levels of cannabis use (r = -.77, p < .001) and positively associated with age of onset of cannabis use (r = .51, p = .027) but was not associated with cannabis-induced psychotic-like symptoms (r = .32, p = .19).
  
  
  CONCLUSIONS
  These findings indicate that chronic cannabis use is associated with reduced dopamine synthesis capacity and question the hypothesis that cannabis increases the risk of psychotic disorders by inducing the same dopaminergic alterations seen in schizophrenia.
authors.affiliation: Psychiatric Imaging Group, Medical Research Council Clinical Sciences Centre, Institute of Clinical Sciences, Hammersmith Hospital, Imperial College London; Department of Psychosis Studies, Institute of Psychiatry, King's College London (King's Health Partners), London, United Kingdom.
authors.forename: Michael A P
authors.initials: MA
authors.lastname: Bloomfield
authors.affiliation: Clinical Psychopharmacology Unit, Division of Psychology and Language Sciences, University College London.
authors.forename: Celia J A
authors.initials: CJ
authors.lastname: Morgan
authors.affiliation: Psychiatric Imaging Group, Medical Research Council Clinical Sciences Centre, Institute of Clinical Sciences, Hammersmith Hospital, Imperial College London; Department of Psychosis Studies, Institute of Psychiatry, King's College London (King's Health Partners), London, United Kingdom.
authors.forename: Alice
authors.initials: A
authors.lastname: Egerton
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's College London (King's Health Partners), London, United Kingdom.
authors.forename: Shitij
authors.initials: S
authors.lastname: Kapur
authors.affiliation: Clinical Psychopharmacology Unit, Division of Psychology and Language Sciences, University College London.
authors.forename: H Valerie
authors.initials: HV
authors.lastname: Curran
authors.affiliation: Psychiatric Imaging Group, Medical Research Council Clinical Sciences Centre, Institute of Clinical Sciences, Hammersmith Hospital, Imperial College London; Department of Psychosis Studies, Institute of Psychiatry, King's College London (King's Health Partners), London, United Kingdom. Electronic address: oliver.howes@csc.mrc.ac.uk.
authors.forename: Oliver D
authors.initials: OD
authors.lastname: Howes
mesh_terms: D002188:Cannabis / Q000009:adverse effects*; D016022:Case-Control Studies; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives; D004298:Dopamine / Q000096:biosynthesis*; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D059907:Functional Neuroimaging; D006801:Humans; D008297:Male; D002189:Marijuana Abuse / Q000000981:diagnostic imaging / Q000378:metabolism*; D049268:Positron-Emission Tomography; D011605:Psychoses, Substance-Induced / Q000000981:diagnostic imaging / Q000378:metabolism*; D055815:Young Adult
chemical_list: C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine; D004298:Dopamine
keywords: Addiction; dependence; dopamine; drugs; imaging; psychosis